Certain xanthine derivatives have been previously used for providing antiasthmatic bronchodilating therapeutic activity. For example, Enprofylline (3-propylxanthine) and theophylline (1,3-dimethylxanthine) are both known antiasthmatics and bronchodilators. Allergy 1983, 38, 75-79 analyzes the bronchospasmolytic activity of Enprofylline, while Medical Hypotheses 8 (1962): 515-526 observes that Enprofylline is four to five times more potent than theophylline, and does not exhibit the adenosine antagonistic activity of theophylline.
However, Enprofylline possesses a disadvantageously short half-life of less than two hours, and also retains an extremely undesirable emetic effect, as is the case with theophylline.
Only one particular 1-unsubstituted thioxanthine derivative, notably 3-isobutyl-6-thioxanthine, has been prepared and examined for bronchodilating activity (Brit. J. Pharmacol. (1961), 17, 196-207). This compound (Compound No. 30 in Table 4) was tested along with 6-thiotheobromines (3,7-disubstituted 6-thioxanthines) and 6-thiocaffeines (1,3,7-trisubstituted 6-thioxanthines). Only two experiments examining the bronchodilating activity of this compound were carried out, and it was noted that the number of experiments carried out was small and the data had not been subjected to any statistical examination.
It has now been surprisingly found that certain 6-thioxanthine derivatives not only result in improved bronchodilating activity, but also result in reduced side effects while having improved half-life over previously-used corresponding xanthine derivative bronchodilators.